title: Trypsin is the culprit of multiple organ injury with severe acute pancreatitis.
abstract: The consistently high proportion of early deaths in patients with severe acute pancreatitis (SAP) has been associated mainly with the development of multiple organ dysfunction syndromes (MODS). So far, scholars believed that the main reasons of MODS with SAP are systemic microcirculation dysfunction and inflammatory mediator induced cascading effect on the basis of pancreas digesting itself. However, there is some special pathological phenomenon in the process of SAP which could not be explained by current theories. First, it has been evident that the pancreatic tissue bleeding and necrosis is special pathological change in pancreas autodigestive effect from digestive enzymes such as trypsin in SAP. However, we found that the liver, the lung, the intestine, the brain and the kidney have the same pathological changes in experimental animal models of SAP. Secondly, unlike the general inflammatory response, a significantly amount of bloody ascites and pleural effusion was often in patients with SAP and in experimental SAP animal models. It indicates that the vascular permeability significantly increased leading to the red blood cells extravasation. Thirdly, apart from dual blood supply, liver bears a strong compensatory function. However, liver has the highest incidence of injury in SAP when compared with other organs. In addition, we found a very interesting phenomenon after reading texts and clinical records. From the pancreatic venous drainage from the point of view, the farther the organ from the pancreas, the lower injury incidence rate observed. How to explain these mysteries? We postulate that the trypsin is the culprit of multiple organs dysfunction in SAP. The activated trypsin destroy the pancreas itself, causing pancreatic tissue bleeding and necrosis, at the same time, through venous flow it flow into the blood circulation and destroy the vascular endothelial barrier, leading to highly increased vascular permeability. So, a large number of bloody exudates leakages from the vessels, resulting in patients early circulatory disorders, multiple organ bleeding, bloody pleural effusion and ascites. This pathological change is the most apparent in the liver because the liver is the first organ to receive the pancreatic venous flow having the highest concentration of trypsin. Thus, if the quantity of trypsin decreases in blood, its ability to damage other organs also shows a trend of gradually reducing. These mysteries can be explained by this hypothesis and might help us to understand more clearly about the mechanism of SAP-associated MODS.
authors.affiliation: Department of Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
authors.forename: Huanchen
authors.initials: H
authors.lastname: Sha
authors.forename: Qingyong
authors.initials: Q
authors.lastname: Ma
authors.forename: Rajiv Kumar
authors.initials: RK
authors.lastname: Jha
mesh_terms: D006801:Humans; D008099:Liver / Q000187:drug effects / Q000473:pathology; D009102:Multiple Organ Failure / Q000209:etiology* / Q000473:pathology; D009336:Necrosis / Q000139:chemically induced; D019283:Pancreatitis, Acute Necrotizing / Q000150:complications* / Q000473:pathology; D014357:Trypsin / Q000633:toxicity*
chemical_list: D014357:Trypsin